Compendial Methods: Suitability Verification, Challenges and Recommendations for Proteins

Abstract

Compendial testing methods are not required to be fully validated but their suitability should be verified under actual conditions of use. This requirement is established in 21 CFR 211.194(a)(2) of the current Good Manufacturing Practice regulations in United States. ANVISA (Agéncia Nacional de Vigiláncia Sanitária) also requires that compendial analytical methods shall have their suitability demonstrated for the intended use by a partial validation study. Suitability verification or partial validation can be divided into two major categories: visual and instrumental methods. For visual methods, the color and clarity interferences should be evaluated. If the color or clarity/opalescence of the sample is outside of the range of the Pharmacopeia standards/reference solutions, the validity of test results should be evaluated. Specificity is usually waived since the methods are not specific to products, and accuracy/precision can be addressed by comparing results from analyst to analyst. For instrument methods, specificity can also be waived for certain assays. Accuracy is addressed by implementation of instrument calibration or/and method control. Precision is required either in suitability verification or performed when testing the samples. Here the approaches of suitability verifications and scientific rationales for compendial methods are presented for Visible Particulates, Sub-Vis Particles, pH, Osmolality, Color and Clarity/Opalescence. Current challenges and recommendations are also discussed for each method.